Transplantation of bone marrow and whole organs, such as the lung, continue to show considerable variation in survival despite improving tissue typing methods. Well matched grafts on occasion reject and mismatched grafts survive. These variations in results are probably accounted for by determinants of histocompatibility which cannot be measured by current techniques. The Cooperstown Beagle Colony with its selected lines of beagle dogs and the breeding records available will be used to study this problem. We have been able to produce long surviving and functioning mismatched lung allografts in animals treated with autologous bone marrow harvest, lethal total-body irradiation, autologous marrow reinfusion, and methotrexate during the first postoperative week. No immuno-suppression therapy is given after the first week post-transplant. We plan to study the immunologic alterations which have occurred in these animals by serial determinations of the donor specific antibody, migration inhibition factor, mixed lymphocyte culture, primed lymphocyte test, and other tests as they become available to evaluate the alterations which have occurred to allow specific mismatched allograft survival. These tools will be used to further elucidate the determinants of histocompatibility of our typing sera and hopefully will lead to the development of more specific agents in the future.